GLYCOGEN SYNTHESIS DR AQSA MALIK BIOCHEMISTRY Glycogen is

GLYCOGEN SYNTHESIS DR AQSA MALIK BIOCHEMISTRY

�Glycogen is the branched polymer of α-D- glucose. �It is the main storage form of carbohydrates in the animals. �It occurs mainly in the liver and muscles. �Muscle glycogen is the readily available form of glucose. �Liver glycogen is the storage form and maintain blood glucose levels. �After 12 -18 hours of fast liver glycogen is totally depleted. �The function of muscle glycogen is to provide fuel reserve for the synthesis of ATP during muscle contraction.

Structure of Glycogen �Glycogen is a branched chain homopolysaccharide made exclusively from α D- glucose. �The primary glycosidic bond is an α(1 -4) linkage. � There is a branch after an average of 8 - 10 glucose residues. �These molecules of glycogen exist in the form of glycogen granules in the cytoplasm. �Enzymes of synthesis and degradation are present in the cytoplasm

Glycogen Stores �During the well fed state liver glycogen stores are increased. �And these stores are depleted in the fasting state. �Muscle glycogen stores are not affected by short periods of fasting and are moderately affected by prolonged fasting. �Synthesis and degradation are two processes that occur continuously.

GLYCOGENESIS �Glycogen is synthesized from molecules of α Dglucose. �Glycogenesis occurs in the cytosol. �It requires ATP and UTP(uridine triphosphate).

Synthesis of UDP- glucose �Glucose is Phosphorylated to glucose-6 PO 4. � This reaction is catalyzed by hexokinase in muscle and glucokinase in the liver. Glucose G 6 P

�Glucose 6 phosphate is isomerized to glucose 1 phosphate. �Enzyme is phosphoglucomutase. �Glucose 1, 6 bisphosphate is an intermediate.

�Glucose 1 phosphate reacts with uridine triphosphate(UTP) to form the active nucleotide uridine diphosphate glucose(UDPGlc) and pyrophosphate. �Enzyme is - UDPGlc pyrophosphorylase

�High energy bond in pyrophosphate(PPi) is hydrolyzed to two inorganic phosphates. �Enzyme- Pyrophosphatase.

Synthesis of a Primer �Glycogen synthase is responsible for making the α(14) linkages in the glycogen. �Free glucose cannot be used to initiate chain synthesis. �It can only elongate already existing chains of glucose.

�A fragment of glycogen can serve as a primer in cells where glycogen stores are not totally depleted. �In the absence of glycogen fragment, a protein called glycogenin serve as an acceptor of glucose residue. �It is glycosylated on a specific tyrosine residue, i. e. the initial glucosyl unit is attached here.

�Transfer of the first few molecules of glucose from UDP- glucose to glycogenin are catalyzed by glycogenin itself. �The short chain that is formed serve as an acceptor of future glucose residues. �Glycogenin remains associated with the completed glycogen molecule.

Elongation of Glycogen Chain �UDP- molecule transfers the glucose molecule to the non reducing end of the growing chain. �Glycosidic bond is formed between C 1 of the activated glucose of UDPGlc and C 4 of a accepting glucose �UDP is liberated.

�The enzyme responsible for making α(1 -4) linkages is: Glycogen Synthase. �UDP can be converted back to UTP by nucleoside diphosphate kinase. UDP+ATP UTP+ADP

Formation of Branches �Glycogen is a highly branched structure. �On average after eight glucosyl residues one branch occurs. �This makes it more soluble. �Branching also increases the non-reducing ends to which more glucose residues can be added. �This increases the size of the molecule.

�Branches are made by the action of branching enzyme: Amylo α(1 -4) - α(1 -6) Transglucosidase �This enzyme transfers a chain of five – eight glucosyl residues from the non-reducing end of the glycogen chain (breaking α(1 -4) bond) to another residue on the chain and attaches it by α(1 -6) linkage. �Further elongation is done by Glycogen Synthase.